Vascular systems are essential for the growth and development of most animals larger than a few centimeters in size because diffusion is inadequate. Members of the Cnidaria, one of the earliest animal phyla, exhibit primitive vascular systems. Colonial cnidarians consist of polyps connected to one another by a common vascular system that integrates colony-wide behavior. Polyps gather and distribute food by pumping it through the gastrovascular system. Vascular transport is sensitive to food availability, oxygen tension and other environmental factors, and vascular architecture. Colony form is inextricably linked to gastrovascular transport and, consequently, plasticity of colony form is considerable and can be adaptive. The goal of the proposed project is to determine if mechanisms regulating vascular development and its plasticity in hydrozoans represent shared primitive characters of metazoans. This objective will be met by testing the following hypotheses: (1) Hydrozoan colony form is plastic in response to oxygen tension (pO2), and manipulations of seawater viscosity that alter shear stress on endodermal cells of stolons. (2) Rates of polyp formation, stolon branching and mitosis of stolon endodermal cells differ with the length and architecture of the stolon on which they reside. (3) Mitotic rates of endodermal cells lining the lumen of stolons increase in response to hypoxia and vascular shear stress. (4) Expression of HIF-1 alpha, VEGF, and matrix metalloproteinase gene homologues increase in response to hypoxia and vascular shear stress and are, therefore, consistent with roles regulating growth and branching of stolons. If vascular development of hydrozoans and vertebrates are regulated by the same mechanisms, the long-term goal is to develop colonial hydrozoans as alternative and complementary models to those of vertebrates for studies of vascular function and its pathologies. Indeed, the relevance of this research to public health lies in the potential for hydrozoan gastrovascular systems to serve as models for studies of human vascular function because of evolutionary conservation of developmental signaling pathways triggered by physiological responses. The practical benefits of utilizing them as models include in vivo experimentation, low cost, clonal replication, and few ethical constraints.